A mutation (rd) which causes degeneration of all photoreceptor cells in the retina is transmitted as an autosomal recessive characteristic of C3H mice. While ultrastructural deterioration of the photoreceptor cells occurs in the second postnatal week, morphological and biochemical abnormalities in the photoreceptor cells have been observed prior to the onset of their degeneration. The postnatal development of photoreceptor synapses in the normal retina involves the following sequence: apposition of synaptic elements at 4 days, a dyad configuration involving horizontal extensions by 8 days and the appearance of a central process to achieve a mature triad configuration by 15 days. In the C3H retina, apposition and dyad formation appears normal but few photoreceptor terminals mature beyond the dyad stage. These observations suggest that the differentiation of the photoreceptor cells is arrested near the end of the first postnatal week. Biochemical studies of cAMP metabolism indicate further that the photoreceptor cells are deficient from the 7th postnatal day, in a phosphodiesterase (PDE) which shows a high Km for cAMP. A PDE which exhibits a low Km for cAMP is normal and concentrated in the inner layers of the C3H retina. The specific PDE classes have been separated by electrophoresis and identified by a histochemical staining technique. In the developing C3H retina, adenyl cyclase activity and the content of cAMP also become abnormal in the second postnatal week. The data suggest that during this period there is an enhanced rate of cAMP synthesis in the inner layers of the C3H retina. A comparative biochemical investigation of protein synthesis in developing DBA and C3H retinae is also in progress. This study will investigate the rate of incorporation of radioactive amino acids in vivo and in vitro, into the total protein fraction of retinae and into individual protein groups which are separated by polyacrylamide gel electrophoresis.